Phthalide derivatives represented by the general formula (IV): ##STR2## wherein R.sup.1 to R.sup.7 are independently selected from lower alkyl groups, and either R.sup.5 and R.sup.6 or R.sup.6 and R.sup.7 may otherwise form together with each other a methylene group, for example tritoqualine, have been used as an antiallergic agent.
Generally, the phthalide derivatives of the general formula (IV) may be prepared by the reaction of nitrophthalides represented by the general formula (I): ##STR3## wherein R.sup.1 to R.sup.3 are as defined above, with isoquinolines represented by the general formula (II): ##STR4## wherein R.sup.4 to R.sup.7 are as defined above, to produce phthalideisoquinolines represented by the general formula (III): ##STR5## wherein R.sup.1 to R.sup.7 are as defined above, followed by reduction of the phthalideisoquinolines.
The nitrophthalides of the general formula (I) have hitherto been prepared by reacting phthalides represented by the general formula (V): ##STR6## wherein R.sup.l to R.sup.3 are as defined above with fuming nitric acid: see British Pat. No. 873,935. In this process, however, a satisfactory yield has not always been attained
On the other hand, the reaction of the nitrophthalides of the general formula (I) with the isoquinolines of the general formula (II) for producing the phthalideisoquinolines of the general formula (III) has been carried out in ethanol, as shown in British Pat. No. 873,935. In this process, also, only unsatisfactory yield is usually obtained.
The present inventors have made great efforts to improve the yields of these reactions and now found that the use of nitrate salts of specified metals in the reaction of the phthalides of the general formula (V) and the use of methanol in the reaction of the nitrophthalides of the general formula (I) with the isoquinolines of the general formula (II) give markedly good results, which have led us to the present invention.